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Updated: Nov 4, 2025
A Thrombotic Stroke Model Based On Transient Cerebral Hypoxia-ischemia
Published on: August 18, 2015
Translational Block in Stroke: A Constructive and "Out-of-the-Box" Reappraisal
Athanasios Lourbopoulos1,2,3, Iordanis Mourouzis1, Christodoulos Xinaris4,5
1Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Abstract:
Why can we still not translate preclinical research to clinical treatments for acute strokes? Despite > 1000 successful preclinical studies, drugs, and concepts for acute stroke, only two have reached clinical translation. This is the translational block. Yet, we continue to routinely model strokes using almost the same concepts we have used for over 30 years. Methodological improvements and criteria from the last decade have shed some light but have not solved the problem. In this conceptual analysis, we review the current status and reappraise it by thinking "out-of-the-box" and over the edges. As such, we query why other scientific fields have also faced the same translational failures, to find common denominators. In parallel, we query how migraine, multiple sclerosis, and hypothermia in hypoxic encephalopathy have achieved significant translation successes. Should we view ischemic stroke as a "chronic, relapsing, vascular" disease, then secondary prevention strategies are also a successful translation. Finally, based on the lessons learned, we propose how stroke should be modeled, and how preclinical and clinical scientists, editors, grant reviewers, and industry should reconsider their routine way of conducting research. Translational success for stroke treatments may eventually require a bold change with solutions that are outside of the box.
Insights
Despite over 1000 successful preclinical studies, acute stroke treatments struggle with clinical translation. This analysis explores reasons for this "translational block" and proposes innovative research models for future success.
Area of Science:
- Neuroscience
- Translational Medicine
- Clinical Neurology
Background:
- Acute stroke research faces a significant
- translational block
- with over 1000 preclinical studies yielding few clinical treatments.
- Current stroke models have remained largely unchanged for over 30 years, hindering progress.
Purpose of the Study:
- To analyze the reasons behind the translational failures in acute stroke research.
- To identify common denominators in translational challenges across scientific fields.
- To explore successful translation strategies in related neurological conditions.
Main Methods:
- Conceptual analysis of existing preclinical and clinical stroke research.
- Comparative analysis with translational successes in migraine, multiple sclerosis, and hypoxic encephalopathy.
- Reappraisal of current stroke modeling and research paradigms.
Main Results:
- Identified persistent translational failures in acute stroke despite extensive preclinical data.
- Highlighted commonalities in translational blocks across different scientific disciplines.
- Observed successful translation in other neurological areas and secondary stroke prevention.
Conclusions:
- Current stroke research models and methodologies are insufficient for successful clinical translation.
- Adopting an "out-of-the-box" perspective and learning from other fields is crucial.
- A paradigm shift in how stroke is modeled and researched is necessary for future therapeutic breakthroughs.
